Photopheresis has been claimed to have immune-modulat-ing effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on the balance of Th1-and Th2-like cytokines. Ten children with newly diagnosed type 1 diabetes (10-17 y) were treated with five double treatments of photopheresis and 10 children matched for disease, age, and gender were given placebo tablets and sham pheresis. Expression of IFN-γ and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-γ , IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). Photopheresis changed antigen-stimulated immune balance in line with a Th2-like shift. Thus, the ratio of IFN-γ /IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD 65 was reduced after treatment in the photopheresis group. The IFN-γ /IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. Photopheresis has an immune-modulating effect in children with type 1 diabetes, causing a Th2-like deviation. Photopheresis has been claimed to have immune-modulat-ing effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on the balance of Th1-and Th2-like cytokines . Ten children with newly diagnosed type 1 diabetes (10-17 y) were treated with five double treatments of photopheresis and 10 children matched for disease, age, and gender were given placebo tablets and sham pheresis. Expression of IFN-γ and IL- 4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-γ, IL-10, and IL-13 in cell- culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (aa 247-279), the ABBOS peptide (aa 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). Photopheresis changed antigen-stimulated immune balance in line with a Th2- the ratio of IFN-γ / IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD 65 was reduced after treatment in the photopheresis group. The IFN-γ / IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group Photopheresis has an immune-modulating effect in children with type 1 diabetes, causing a Th2-like deviation.